Regulation of osteoclastogenesis by antisense oligodeoxynucleotides specific to zinc finger nuclear transcription factors Egr-1 and WT1 in rat bone marrow culture system

Endocrinology. 1997 Oct;138(10):4384-9. doi: 10.1210/endo.138.10.5466.


Differentiation of osteoclasts is defined by the transcription factors expressed in response to bone microenvironments. In this work, we examined the effects of an expressional blockage of Egr-1 and/or WT1 on the differentiation of osteoclasts using specific antisense oligodeoxynucleotides (ODN). In a culture system forming preosteoclast-like cells (POC) from rat bone marrow cells depleted of marrow stromal cells, POC formation was markedly stimulated by the addition of Egr-1 antisense ODN compared to that in cultures in which sense ODN was added, whereas Egr-1 antisense ODN inhibited the formation of macrophage-like cells. The formation of multinucleated osteoclast-like cells was also stimulated by the addition of Egr-1 antisense ODN in whole bone marrow cultures. In contrast, WT1 antisense ODN did not affect POC formation induced by the treatment with Egr-1 antisense ODN; however, WT1 antisense ODN dramatically suppressed the formation of osteoclast-like multinucleated cells induced by the blockage of Egr-1 expression using Egr-1 antisense ODN. These data suggest that Egr-1 acts as the suppressor, not as the inducer, in osteoclastogenesis. The findings also suggested that WT1 could be involved in the multinucleation step of osteoclastogenesis, at least when Egr-1 expression was blocked.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Bone Marrow / chemistry
  • Bone Marrow / drug effects
  • Bone Marrow Cells*
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cells, Cultured
  • DNA / analysis
  • DNA / chemistry
  • DNA / genetics
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology
  • Early Growth Response Protein 1
  • Immediate-Early Proteins*
  • Male
  • Oligonucleotides, Antisense / chemistry
  • Oligonucleotides, Antisense / genetics
  • Oligonucleotides, Antisense / pharmacology*
  • Osteoclasts / chemistry
  • Osteoclasts / cytology*
  • Osteoclasts / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Retroviridae Proteins, Oncogenic / chemistry*
  • Retroviridae Proteins, Oncogenic / genetics
  • Retroviridae Proteins, Oncogenic / physiology
  • Stem Cells / chemistry
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Transcription Factors / chemistry*
  • Transcription Factors / genetics
  • Transcription Factors / physiology
  • WT1 Proteins
  • Zinc Fingers / genetics*


  • DNA-Binding Proteins
  • Early Growth Response Protein 1
  • Egr1 protein, rat
  • Immediate-Early Proteins
  • Oligonucleotides, Antisense
  • Retroviridae Proteins, Oncogenic
  • Transcription Factors
  • WT1 Proteins
  • DNA